Methylation markers for anal cancer screening: A repeated cross-sectional analysis of people living with HIV, 2015-2016.

People living with HIV (PLWH) are at highest risk of anal cancer and will benefit from optimized screening for early disease detection. We compared host DNA methylation markers in high-grade squamous intraepithelial lesions (HSIL) versus samples negative for intraepithelial lesions (NILM) or low-grade intraepithelial lesions (LSIL) in PLWH. We recruited PLWH identifying as male aged ≥18 years undergoing high-resolution anoscopy (HRA) in Seattle, Washington, 2015-2016. Anal brush samples were collected for HPV detection, genotyping, and pyrosequencing methylation (host genes ASCL1, PAX1, FMN2, and ATP10A); clinical data were abstracted from medical records. We assessed associations between methylation and presence and extent of HSIL using generalized estimating equation logistic regression, adjusting for age, CD4 count and HIV viral load. Marker panels using HPV DNA and methylation were also evaluated to predict prevalent HSIL. We analyzed 125 samples from 85 participants (mean age 50.1; standard deviation 11.0 years). ASCL1 (adjusted odds ratio [aOR] per 1 unit increase mean percent methylation: 1.07, 95% CI: 1.01-1.13) and FMN2 (aOR per 1 unit increase mean percent methylation: 1.14, 95% CI: 1.08-1.20) methylation were significantly associated with HSIL versus NILM/LSIL. ASCL1 (aOR: 1.06, 95% CI: 1.01-1.11) and FMN2 (aOR: 1.13, 95% CI: 1.08-1.17) methylation were positively associated with increasing HSIL extent. A panel combining methylation (ASCL1 and FMN2) and HPV DNA (HPV16, HPV18, and HPV31) demonstrated best balance of sensitivity (78.2%) and specificity (73.9%) for HSIL detection compared with methylation or HPV alone. Increasing levels of DNA methylation of ASCL1 and FMN2 were positively associated with HSIL detection in PLWH. Host gene methylation testing shows promise for HSIL screening and triage.

Advancing Adolescent HIV Prevention and Care Through Implementation Science: An Agenda for Combating the Global AIDS Epidemic in Sub-Saharan Africa.

AIDS continues to be a major driver of adolescent mortality in Sub-Saharan Africa. Despite evidence of efficacy in this population, many efforts to address adolescent HIV have had limited impact across the region because of difficulty with implementation. The field of implementation science holds promise for addressing these challenges. The Fogarty-led Adolescent HIV Prevention and Treatment Implementation Science Alliance (AHISA) creates a platform for bidirectional learning between researchers and the users of research evidence that promotes the use of implementation science to strengthen adolescent HIV prevention and care across Africa. The unique contributions of AHISA are reflected in this supplement's articles which represent the collective learning of the Alliance; illustrate the value of implementation science in the context of adolescent HIV; and identify critical research gaps that should be addressed by implementation science in the future.

Navigating the Storm of COVID-19 Literature Through Academic-Practice Partnership in Washington State: The COVID-19 Literature Situation Report.

CONTEXT: Shortly after the first COVID-19 case in the United States was identified in Washington, the Washington State Department of Health (WA DOH) determined that real-time knowledge of scientific findings related to SARS-CoV-2 was critical for an effective response. Epidemiologists at the WA DOH established the Daily Literature Situation Report (Lit Rep), within the agency's incident management team, to support public health and state leaders in evidence-based decision making. However, from January to May, the scale of the pandemic response and daily volume of emerging information grew beyond the capacity of the WA DOH epidemiology team tasked with gathering, reviewing, summarizing, and disseminating it daily. OBJECTIVE: To ensure public health leaders maintained awareness of the rapidly evolving scientific literature during the pandemic to support evidence-based practice. DESIGN: The WA DOH contracted the University of Washington (UW) Alliance for Pandemic Preparedness to assemble a team of faculty and students to continue producing the Lit Rep. MAIN OUTCOME: In addition to the daily Lit Rep, the UW team developed in-depth reports addressing questions from public health leadership and further evolved the methodology for the daily reports to support long-term sustainability and broader accessibility. RESULTS: Throughout its existence, the Lit Rep had summarized more than 4300 articles from more than 150 000 citations and had more than 5600 subscribers from public health practice, academia, and the general public, both domestic and international. CONCLUSIONS: The flexible Lit Rep model sets a standard for responding to emerging public health threats and communicating complex scientific information to government leaders, public health staff, and other interested parties. The WA DOH and the UW have exemplified how a mutually beneficial partnership can be established to support more effective public health practice based on real-time evidence both during a crisis and potentially for future public health challenges.

Training tomorrow's leaders in global health: impact of the Afya Bora Consortium Fellowship on the careers of its alumni.

BACKGROUND: Effective leadership is a cornerstone of successful healthcare delivery in resource limited settings throughout the world. However, few programs in Africa prepare healthcare professionals with the leadership skills vital to the success of the healthcare systems in which they work. One such program, the Afya Bora Consortium Fellowship in Global Health Leadership, has been training health professionals since 2011. The purpose of this study was to assess what career changes, if any, the Afya Bora Fellowship's alumni have experienced since completing the fellowship, and to describe those changes. METHODS: The Afya Bora Fellowship is a multidisciplinary, one-year training program that teaches health professionals leadership skills through didactic and experiential learning in four African countries. Between January 2011 and June 2013 the consortium trained 42 nurses and doctors. In November 2013, an electronic survey was sent to all alumni to assess their performance in the workplace post-fellowship. RESULTS: Thirty-one (74 %) of 42 alumni completed surveys. Twenty-one (68 %) reported changes to their position at work; of those, sixteen (76 %) believed the change was due to participation in the fellowship. All alumni reported improved performance at work, and cited the application of a wide range of fellowship skills, including leadership, research, communication, and mentoring. Twenty-six (84 %) alumni spearheaded improvements in their workplaces and almost all (97 %) remained in contact with colleagues from the fellowship. Among the respondents there were five publications, nine manuscripts in preparation, and three international conference presentations. CONCLUSIONS: Afya Bora alumni overwhelmingly reported that the one year fellowship positively influenced both their work and career trajectory. Training health professionals in leadership skills through didactic modules with the opportunity to apply learned skills at attachment sites in the Afya Bora Fellowship has an impact on performance in the workplace and the potential to improve long-term institutional capacity.

Impact of Vaccination and Nonpharmaceutical Interventions With Possible COVID-19 Viral Evolutions Using an Agent-Based Simulation.

Introduction: The COVID-19 pandemic continues with highly contagious variants and waning immunity. As the virus keeps evolving to be more infectious and immune evasive, some question whether the COVID-19 pandemic can be managed through sustainable public health measures. Methods: We developed an agent-based simulation to explore the impact of COVID-19 mutations, periodic vaccinations, and nonpharmaceutical interventions on reducing COVID-19 deaths. The model is calibrated to the greater Seattle area by observing local epidemic data. We perform scenario analyses on viral mutations that change infectiousness, disease severity, and immune evasiveness from previous infections and vaccination every 6 months. The simulation is run until the end of year 2023. Results: Variants with increased infectivity or increased immune evasion dominate previous strains. With enhanced immune protection from a pancoronavirus vaccine, the most optimistic periodic vaccination rate reduces average total deaths by 44.6% compared with the most pessimistic periodic vaccination rate. A strict threshold nonpharmaceutical intervention policy reduces average total deaths by 71.3% compared with an open society, whereas a moderate nonpharmaceutical intervention policy results in a 33.6% reduction. Conclusions: Our findings highlight the potential benefits of pancoronavirus vaccines that offer enhanced and longer-lasting immunity. We emphasize the crucial role of nonpharmaceutical interventions in reducing COVID-19 deaths regardless of virus mutation scenarios. Owing to highly immune evasive and contagious SARS-CoV-2 variants, most scenarios in this study fail to reduce the mortality of COVID-19 to the level of influenza and pneumonia. However, our findings indicate that periodic vaccinations and a threshold nonpharmaceutical intervention policy may succeed in achieving this goal. This indicates the need for caution and vigilance in managing a continuing COVID-19 epidemic.

The utility of a composite biological endpoint in HIV/STI prevention trials.

A human immunodeficiency virus (HIV) as a biological endpoint in HIV prevention trials may not be feasible, so investigators have used surrogate biological outcomes. In a multisite trial, the epidemiology of STIs may be different across sites and preclude using one STI as the outcome. This study explored using a composite STI outcome to address that problem. The combined biological endpoint was the incidence of any of six new STIs (chlamydia, gonorrhea, trichomonas (women only), syphilis, herpes simplex virus type 2 infection and HIV) during a 24-month follow up period. We investigated how a composite STI outcome would perform compared to single and dual STI outcomes under various conditions. We simulated outcomes for four populations that represented a wide range of sex and age distributions, and STI prevalences. The simulations demonstrated that a combined biologic outcome was superior to single and dual STI outcomes in assessing intervention effects in 82 % of the cases. A composite biological outcome was effective in detecting intervention effects and might allow more investigations to incorporate multiple biological outcomes in the assessment of behavioral intervention trials for HIV prevention.

Trends in the Use of Face Coverings in Publicly Accessible Spaces During the COVID-19 Pandemic, King County, Washington, November 2020-May 2021.

OBJECTIVES: Appropriate face covering use at public venues can help mitigate the transmission of SARS-CoV-2 in the absence of widespread vaccination and provide protection when viral variants become more infectious. The objective of this study was to evaluate compliance with a statewide face mask mandate by examining trends in face covering use in publicly accessible spaces in King County, Washington. METHODS: From November 27, 2020, through May 11, 2021, we conducted a repeated cross-sectional observational study of face covering use across publicly accessible venues (eg, grocery and convenience stores, airport, transit center, post office). Trained observers recorded perceived sex, estimated age group, and face covering use. We calculated estimates of overall face covering use and prevalence ratios (PRs) with 95% CIs. RESULTS: We observed 9865 people in 53 unique venues during 229 observation intervals during 6 observation periods. Correct face covering use was 87.2% overall and lowest at semi-outdoor venues such as transit hubs (78.1%) and the pick-up curb of Seattle-Tacoma International Airport (69.0%). Correct face covering use was lowest among men (PR = 1.42; 95% CI, 1.27-1.58) and among people aged 2-11 years (PR = 2.74; 95% CI, 2.37-3.17) and 12-17 years (PR = 1.36; 95% CI, 1.07-1.72). Compliance declined among adults aged ≥60 years and among younger age groups before vaccine eligibility. CONCLUSIONS: Overall compliance with the statewide face mask mandate in King County was high. Layered mitigation strategies, including but not limited to the use of face coverings, and methods to assess adherence to them are crucial to preventing SARS-CoV-2 transmission.

Combination HIV prevention: significance, challenges, and opportunities.

No single HIV prevention strategy will be sufficient to control the HIV pandemic. However, a growing number of interventions have shown promise in partially protecting against HIV transmission and acquisition, including knowledge of HIV serostatus, behavioral risk reduction, condoms, male circumcision, needle exchange, treatment of curable sexually transmitted infections, and use of systemic and topical antiretroviral medications by both HIV-infected and uninfected persons. Designing the optimal package of interventions that matches the epidemiologic profile of a target population, delivering that package at the population level, and evaluating safety, acceptability, coverage, and effectiveness, all involve methodological challenges. Nonetheless, there is an unprecedented opportunity to develop "prevention packages" that combine various arrays of evidence-based strategies, tailored to the needs of diverse subgroups and targeted to achieve high coverage for a measurable reduction in population-level HIV transmission. HIV prevention strategies that combine partially effective interventions should be scaled up and evaluated.

COVID-19 Pandemic Response Simulation in a Large City: Impact of Nonpharmaceutical Interventions on Reopening Society.

As the novel coronavirus (COVID-19) pandemic continues to expand, policymakers are striving to balance the combinations of nonpharmaceutical interventions (NPIs) to keep people safe and minimize social disruptions. We developed and calibrated an agent-based simulation to model COVID-19 outbreaks in the greater Seattle area. The model simulated NPIs, including social distancing, face mask use, school closure, testing, and contact tracing with variable compliance and effectiveness to identify optimal NPI combinations that can control the spread of the virus in a large urban area. Results highlight the importance of at least 75% face mask use to relax social distancing and school closure measures while keeping infections low. It is important to relax NPIs cautiously during vaccine rollout in 2021.

Opportunities and Challenges in North-South and South-South Global Health Collaborations During the COVID-19 Pandemic: The AFREhealth-CUGH Experience (as Reported at the CUGH 2021 Satellite Meeting).

Sustainable and equitable partnerships and collaborations between the Global North and Global South (as well as within the Global South) have been aspirations (if seldom achieved) of the "global health" endeavor over the past couple of decades. The COVID-19 pandemic led to global lockdowns that disrupted international travel and severely challenged these partnerships, providing a critical space for self-reflection on global health as a discipline. One major global north-south partnership is that between the African Forum for Research and Education in Health (AFREhealth) and the Consortium of Universities for Global Health (CUGH). This article reports on a recent Satellite meeting of the AFREhealth-CUGH Working Group (ACWG) at the CUGH 2021 virtual conference in March 2021 that provided insights on North-South and South-South global health partnerships, against the backdrop of the COVID-19 pandemic. The authors describe challenges and opportunities for research and education in these partnerships (as discussed at this ACWG Satellite meeting), and implications for the field of global health going forward as we emerge from the pandemic.

A Framework for Cervical Cancer Elimination in Low-and-Middle-Income Countries: A Scoping Review and Roadmap for Interventions and Research Priorities.

The World Health Organization announced an ambitious call for cervical cancer elimination worldwide. With existing prevention and treatment modalities, cervical cancer elimination is now within reach for high-income countries. Despite limited financing and capacity constraints in low-and-middle-income countries (LMICs), prevention and control efforts can be supported through integrated services and new technologies. We conducted this scoping review to outline a roadmap toward cervical cancer elimination in LMICs and highlight evidence-based interventions and research priorities to accelerate cervical cancer elimination. We reviewed and synthesized literature from 2010 to 2020 on primary and secondary cervical cancer prevention strategies. In addition, we conducted expert interviews with gynecologic and infectious disease providers, researchers, and LMIC health officials. Using these data, we developed a logic model to summarize the current state of science and identified evidence gaps and priority research questions for each prevention strategy. The logic model for cervical cancer elimination maps the needs for improved collaboration between policy makers, production and supply, healthcare systems, providers, health workers, and communities. The model articulates responsibilities for stakeholders and visualizes processes to increase access to and coverage of prevention methods. We discuss the challenges of contextual factors and highlight innovation needs. Effective prevention methods include HPV vaccination, screening using visual inspection and HPV testing, and thermocoagulation. However, vaccine coverage remains low in LMICs. New strategies, including single-dose vaccination could enhance impact. Loss to follow-up and treatment delays could be addressed by improved same-day screen-and-treat technologies. We provide a practical framework to guide cervical cancer elimination in LMICs. The scoping review highlights existing and innovative strategies, unmet needs, and collaborations required to achieve elimination across implementation contexts.

Randomized controlled trials of interventions to prevent sexually transmitted infections: learning from the past to plan for the future.

Globally, sexually transmitted infections (STIs) represent a significant source of morbidity and disproportionately impact the health of women and children. The number of randomized controlled trials testing interventions to prevent STIs has dramatically increased over time. To assess their impact, the authors conducted a systematic review of interventions to prevent sexual transmission or acquisition of STIs other than human immunodeficiency virus, published in the English-language, peer-reviewed literature through December 2009. Ninety-three papers reporting data from 74 randomized controlled trials evaluating 75 STI prevention interventions were identified. Eight intervention modalities were used: behavioral interventions (36% of interventions), vaginal microbicides (16%), vaccines (16%), treatment (11%), partner services (9%), physical barriers (5%), male circumcision (5%), and multicomponent (1%). Overall, 59% of interventions demonstrated efficacy in preventing infection with at least 1 STI. Treatment interventions and vaccines for viral STIs showed the most consistently positive effects. Male circumcision protected against viral STIs and possibly trichomoniasis. Almost two-thirds of behavioral interventions were effective, but the magnitude of effects ranged broadly. Partner services yielded similarly mixed results. In contrast, vaginal microbicides and physical barrier methods demonstrated few positive effects. Future STI prevention efforts should focus on enhancing adherence within interventions, integrating new technologies, ensuring sustainable behavior change, and conducting implementation research.

Evaluating and optimizing the consolidated framework for implementation research (CFIR) for use in low- and middle-income countries: a systematic review.

BACKGROUND: The Consolidated Framework for Implementation Research (CFIR) is a determinants framework that may require adaptation or contextualization to fit the needs of implementation scientists in low- and middle-income countries (LMICs). The purpose of this review is to characterize how the CFIR has been applied in LMIC contexts, to evaluate the utility of specific constructs to global implementation science research, and to identify opportunities to refine the CFIR to optimize utility in LMIC settings. METHODS: A systematic literature review was performed to evaluate the use of the CFIR in LMICs. Citation searches were conducted in Medline, CINAHL, PsycINFO, CINAHL, SCOPUS, and Web of Science. Data abstraction included study location, study design, phase of implementation, manner of implementation (ex., data analysis), domains and constructs used, and justifications for use, among other variables. A standardized questionnaire was sent to the corresponding authors of included studies to determine which CFIR domains and constructs authors found to be compatible with use in LMICs and to solicit feedback regarding ways in which CFIR performance could be improved for use in LMICs. RESULTS: Our database search yielded 504 articles, of which 34 met final inclusion criteria. The studies took place across 21 countries and focused on 18 different health topics. The studies primarily used qualitative study designs (68%). Over half (59%) of the studies applied the CFIR at study endline, primarily to guide data analysis or to contextualize study findings. Nineteen (59%) of the contacted authors participated in the survey. Authors unanimously identified culture and engaging as compatible with use in global implementation research. Only two constructs, patient needs and resources and individual stages of change were commonly identified as incompatible with use. Author feedback centered on team level influences on implementation, as well as systems characteristics, such as health system architecture. We propose a "Characteristics of Systems" domain and eleven novel constructs be added to the CFIR to increase its compatibility for use in LMICs. CONCLUSIONS: These additions provide global implementation science practitioners opportunities to account for systems-level determinants operating independently of the implementing organization. Newly proposed constructs require further reliability and validity assessments. TRIAL REGISTRATION: PROSPERO, CRD42018095762.

Informing Rift Valley Fever preparedness by mapping seasonally varying environmental suitability.

BACKGROUND: Rift Valley Fever (RVF) poses a threat to human and animal health throughout much of Africa and the Middle East and has been recognized as a global health security priority and a key preparedness target. METHODS: We combined RVF occurrence data from a systematic literature review with animal notification data from an online database. Using boosted regression trees, we made monthly environmental suitability predictions from January 1995 to December 2016 at a 5 × 5-km resolution throughout regions of Africa, Europe, and the Middle East. We calculated the average number of months per year suitable for transmission, the mean suitability for each calendar month, and the "spillover potential," a measure incorporating suitability with human and livestock populations. RESULTS: Several countries where cases have not yet been reported are suitable for RVF. Areas across the region of interest are suitable for transmission at different times of the year, and some areas are suitable for multiple seasons each year. Spillover potential results show areas within countries where high populations of humans and livestock are at risk for much of the year. CONCLUSIONS: The widespread environmental suitability of RVF highlights the need for increased preparedness, even in countries that have not previously experienced cases. These maps can aid in prioritizing long-term RVF preparedness activities and determining optimal times for recurring preparedness activities. Given an outbreak, our results can highlight areas often at risk for subsequent transmission that month, enabling decision-makers to target responses effectively.

The arc of HIV epidemics in sub-Saharan Africa: new challenges with concentrating epidemics in the era of 90-90-90.

PURPOSE OF REVIEW: The aim of this review is to examine the emerging results from the HIV universal test and treat (UTT) cluster-randomized trials in sub-Saharan Africa, discuss how expanding access to HIV clinical services is likely to reshape the arc of HIV epidemics, and consider implications for HIV prevention and control strategies in the coming decade. RECENT FINDINGS: The effect of universal HIV testing followed by immediate antiretroviral treatment (ART) on community-level HIV incidence remains unclear upon completion of five randomized trials. Only two of the four trials that measured HIV incidence found significant reductions in community-level incidence. Even in these trials, HIV incidence remained above levels required for epidemic control (≤1 case per 1000 person-years) despite high levels of ART coverage and viral suppression. These findings may indicate that community-delivered HIV services are not reaching the high-frequency transmitters who sustain HIV epidemics and are likely members of marginalized or hard to engage core groups. SUMMARY: With expanded access to HIV services in sub-Saharan Africa, HIV epidemics are transitioning from hyperendemic to declining/endemic epidemic phases, characterized increasingly by the reconcentration of HIV in marginalized or hard to engage core groups. To move toward epidemic control, novel HIV service delivery models and technologies are needed to engage those who continue to drive HIV incidence in this new epidemic phase.